This invention relates to compositions for the treatment of overweight and obesity.
The management of body weight is a complex phenomenon that generally varies according to nutritive equilibrium. The amount of energy introduced with the intake of food and that used by the organism for the maintenance of vital functions (metabolism, respiration, thermoregulation, movement etc.) determines the energetic balance, which, if positive for long-term periods, inevitably leads to increased body weight and obesity.
In the last few years it has been clearly shown that weight-control diets are not efficient by themselves, while the use of drugs against obesity have significant side effects. The main problems associated with the control of body weight are the following:
a) The loss of weight, obtained by a low-calorie diet, gives rise, as a defense mechanism, to an exacerbated attraction for food, especially carbohydrates which are transformed into fat by the organism. Subsequently, the temporary weight loss is replaced by a fast and often uncontrolled weight increase.
b) The mobilization of fats from adipose deposits and their preferential use in metabolic processes occurs with difficulty and represents the hardest problem to face.
Modern research has shown that efficient weight management not only requires a reduction of the amount of energy introduced into the organism through the intake of fats and sugars (low-fat/low-calorie diets), but also the means of mobilizing the fat stored, that is, the use of substances with thermogenic action.
Thermogenesis is a metabolic process consisting of the production of heat by the organism, especially in the muscles and in the adipose tissues, using as energy source the available fat deposits. High thermogenesis allows body weight to decrease without significant variations in the quantity of food intake. The levels of thermogenesis vary from individual to individual, in a genetically predetermined way and for this reason body weight also varies from individual to individual regardless of the energetic limits set by the diet. The processes of thermogenesis are managed by the adrenergic system, through beta-3-adrenergic receptors.
Accordingly, the levels of thermogenesis can be altered with some adrenergic-like substances (adrenergic or sympathomimetic) such as, for instance, ephedrine, synephrine, amphetamine, phenylephrine etc. Adrenergic-like compounds are not very active alone in the activation of thermogenesis, and therefore, they are commonly used together with CNS stimulants, such as the methylxanthines: caffeine, theophylline and theobromine, which have a synergistic action with adrenergic substances.
The main problem associated with this approach consists of the fact that both adrenergic substances and methylxanthines produce significant side effects, particularly at cardiac-circulatory level, interacting with adrenergic receptors different from beta-3 receptors, and their administration is not recommended especially in hypertensive and borderline hypertensionxe2x80x94patients, and may lead to serious adverse reactions. Incidentally, many overweight individuals that would benefit from the stimulation of thermogenesis are also hypertensive. The concomitant use of hypotensive drugs is to be avoided in all cases of borderline hypertension, because of the development of rebound phenomena. Of the natural extracts, Crataegus is known for its bland hypotensive activity. However, the disadvantages of the use of Crataegus are that: i) high dosages are required [approx. 400-800 mg/day]; ii) hypotension is often induced in normotensive patients
Thus, natural alternatives are needed to avoid the side effects of the adrenergic substances used in the weight control management.
The other problem resides in the fact that the use of thermogenic substances alone is not sufficient for an effective long-term management of body weight. The simultaneous administration of other active ingredients is therefore required. For example, one of the substances used in weight control is food fiber. However this supplement must be administered separately since it interferes with the absorption of other nutrients if they are administered together.
The object of this invention is to provide compositions comprising at least one substance selected from the group consisting of ephedrine, pseudo-ephedrine, synephrine, tyramine, octopamine, methyltyramine, horderine, as a chemically pure substance or as a component of an extract of natural origin or any other compounds with adreneric activity, or CNS stimulants, in combination with a Crataegus extract standardized, or not, in flavonoids associated with a Gingko biloba extract standardized, or not, in flavonglucosides.
This Crataegus extract contains flavonoids, and if combined with extract from Gingko biloba containing flavonglucosides, the resulting preparation exhibit unexpected synergistic activity in inhibiting the hypertensive and tachycariac effects of ephedrine and synephrine alone or together with other Central Nervous System stimulants.
This synergistic action is surprising since the same Crataegus extract, if not combined with the extract from Gingko biloba, does not by itself exert such activity at the dosages used and in order to show any anti-hypertensive activity, the dosages of must be 2 to 4 times higher. Moreover, the extracts of Gingko biloba do not exert hypotensive effects at any dosage.
If not otherwise specified, all the reagents used in the trials were obtained from Sigma, Chem. Co., St. Louis, Mo., USA. The extract of Ephedra sinica, standardized in 8% of ephedrine, the extract of Crataegus standardized in 2% flavonoids, the extract of Ginkgo biloba standardized in 24% flavonglucosides and the extract of Citrus aurantium standardized in 4% of synephrine was supplied by the company SOCHIM International, Milan. Exact quantities of the Gingko biloba extract were subsequently added to the extract from Crataegus, thereby obtaining in the course of the experiments one final vegetable composition standardized in 1.65% flavonoids and 6%-flavonglucosides. For convenience, in the description which follows this combination shall be called Oterin(copyright). Therefore Oterin(copyright) is a new extract of Crataegus standardized in 1.65 flavonoids and enriched in 6% flavonglucosides from Gingko biloba.